Electrocyclic reactions enantioselectivity

Within the above context and building on our previous results (Rueping et al. 2005a,b, 2006a-e, 2007a Rueping and Azap 2006), we decided to examine a metal free, BINOL-phosphate catalyzed Nazarov reaction. This would not only be the first example of a Brpnsted acid catalyzed, enantioselective, electrocyclic reaction but would additionally provide a simple and direct route to optically pure cyclopentenones. 

We have developed the first enantioselective Brpnsted acid catalyzed Nazarov reaction. This efficient method is not only the first example of an organocatalytic electrocyclic reaction but it also provides the corre-... 

Electrocyclization reactions of unsaturated esters and enones in solution have led to very low asymmetric inductions, and the origin of the selectivity observed is not completely understood [56-59]. When inclusion complexes (1 1) of 19, 22, and 247 with chiral hosts 241b or c, were irradiated in the solid state, almost complete enantioselectivity was observed (Scheme 39). 

A review which covers sigmatropic rearrangements in addition to Diels-Alder reactions, 1,3-dipolar cycloadditions, electrocyclic reactions, and ene reactions has appeared. The stereochemistry of [3,3]-sigmatropic reactions of chiral carbon compounds has been reviewed, as have diastereoselective Claisen rearrangements of substrates bearing chiral auxiliary and enantioselective variants of achiral substrates. Examples of [3,3]-sigmatropic rearrangements used in the synthesis of various types of 3-chromene derivatives have been reviewed. ... 

Quite recently. Rueping et al reported Nazarov cyclization reaction catalyzed by a phosphoramide (Scheme 2.107) [185]. Although phosphoric acid (41k) is effective for the Nazarov reaction, use of an N-triflyl phosphoramide (50b) improved the enantioselectivity. This is the first example of the enantioselective organocatalytic electrocyclization reaction. 

Next, another work on a Br0nsted acid-catalyzed intramolecular electrocyclization reaction was reported by list [36]. They demonstrated that chiral Bronsted acid 104 could efficiently promote the cycloisomerization of a,P-unsaturated hydrazones 105 to give pyrazoUnes 106 in high yields and with good enantioselectivity (Scheme 36.28). This is also the first example of an organocatalytic asymmetric 671 electrocyclization reaction. 

AB ABCE ABCDE - ABCDEF W-G aldehyde (-)-Strychnine] (27) After his racemic synthesis of strychnine (26), Kuehne also achieved an enantioselective synthesis of (—)-strychnine (Scheme 9). To avoid the low yield conversion of isostrychnine to strychnine, the second approach was directed to the W-G aldehyde. Starting from L-tryptophan methyl ester (86), the cyclization precursor 87 was prepared in seven steps in a similar way as in the previous racemic synthesis. The domino condensation-electrocyclization reaction of 87 with dienal 88 proceeded with quite high diastereoselectivity (>95% de) [AB ABCE, C7 quaternary center] (85). After conversion of the tetracyclic compound 89 to tosylate 92, removal of the benzyl group resulted in the clean formation of the D ring [ABCE ABCDE ]. Unlike in the first synthesis, introduction of the hydroxyethylidene side chain by a Horner-Wadsworth-Emmons reaction of ketone 93 proceeded with high stereoselectivity (E Z = 17 1). Einally, the E isomer 94E was converted to (-)-strychnine via the W-G aldehyde (50). 

Rueping M, leawsuwan W, Antonchick AP, Nachtsheim BJ. Chiral Brpnsted acids in the catalytic asymmetric Nazarov cyclization-the first enantioselective organocatalytic electrocyclic reaction. Angew. Chem. Int. Ed. 2007 46 2097-2100. 

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

In 2004, the group of Sorensen reported an efficient enantioselective total synthesis of (-l-)-harziphilone (6) using an MBFT strategy (Scheme 13.1), which allowed the direct conversion of an acyclic polyunsaturated diketone 1 to the required bicyclic ring system of the target molecule in one step through a DABCO-catalyzed double conjugate addition reaction followed by a 6x-electrocyclization cascade reaction [2]. 

The Nazarov reaction belongs to a type of 4n electrocyclization and can usually be promoted by metal-based catalysts. In 2007, the first enantioselective organo-catalytic Nazarov reaction was reported by Rueping and coworkers [35aj. A chiral N-triflyl-phosphoramide 101 was a better selection for the cyclization of dienone substrates 102, and cyclopentenone products 103 were generated as a diastereo-meric mixture but with excellent enantioselectivity at low catalyst loadings (2 mol%) (Scheme 36.27). 

Recently, Rueping et al. [36] disclosed the first enantioselective Nazarov cyclization reaction organocatalyzed by a chiral Brpnsted acid. The proposed reaction pathway involves a conrotatory 4n electrocyclization of the divinyl ketone 83 leading to the formation of an enol intermediate which is then snbjected to enantioselective protonation by the chiral Brpnsted acid 82b. This electrocyclization-protonation reaction was conducted with various divinyl ketones 83 under optimized conditions, i.e. in the presence of the chiral A -triflyl phosphoramide 82b (5 mol%) in chloroform at -10°C, affording the corresponding cyclopentenones 84 with 67-78% ee (for examples, see 83a-c 84a-c, Scheme 3.44). 

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